Dysbiosis of upper respiratory tract microbiota in elderly pneumonia patients

Abstract

Bacterial pneumonia is a major cause of morbidity and mortality in elderly. We hypothesize that dysbiosis between regular residents of the upper respiratory tract (URT) microbiome, that is balance between commensals and potential pathogens, is involved in pathogen overgrowth and consequently disease. We compared oropharyngeal microbiota of elderly pneumonia patients (n = 100) with healthy elderly (n = 91) by 16S-rRNA-based sequencing and verified our findings in young adult pneumonia patients (n = 27) and young healthy adults (n = 187). Microbiota profiles differed significantly between elderly pneumonia patients and healthy elderly (PERMANOVA, Po0.0005). Highly similar differences were observed between microbiota profiles of young adult pneumonia patients and their healthy controls. Clustering resulted in 11 (sub)clusters including 95% (386/405) of samples. We observed three microbiota profiles strongly associated with pneumonia (Po0.05) and either dominated by lactobacilli (n = 11), Rothia (n = 51) or Streptococcus (pseudo)pneumoniae (n = 42). In contrast, three other microbiota clusters (in total n = 183) were correlated with health (Po0.05) and were all characterized by more diverse profiles containing higher abundances of especially Prevotella melaninogenica, Veillonella and Leptotrichia. For the remaining clusters (n = 99), the association with health or disease was less clear. A decision tree model based on the relative abundance of five bacterial community members in URT microbiota showed high specificity of 95% and sensitivity of 84% (89% and 73%, respectively, after cross-validation) for differentiating pneumonia patients from healthy individuals. These results suggest that pneumonia in elderly and young adults is associated with dysbiosis of the URT microbiome with bacterial overgrowth of single species and absence of distinct anaerobic bacteria. Whether the observed microbiome changes are a cause or a consequence of the development of pneumonia or merely coincide with disease status remains a question for future research.

The dynamics of the pulmonary microbiome during mechanical ventilation in the intensive care unit and the association with occurrence of pneumonia

“…This is in line with previous studies that report that the respiratory microbiome is disturbed markedly during pneumonia 29 30. We extend the finding of the limited studies done in ICU-patients,25 31 32 as no control group was included in those studies and thus it was previously unknown what the ‘normal’ dynamics in the respiratory microbiome were during mechanical ventilation.…”

Respiratory microbiota and lower respiratory tract disease

“…was associated with pneumonia. 46 This result was partly consistent with a pediatric study assessing the association between upper and lower respiratory tract microbiota and pneumonia severity. 66 Presence of Lactobacillales was associated with longer hospital stay in children older than five years of age, but with a less severe pneumonia in under-five children underscoring the importance of age-related host-microbe interactions and immune system dynamics.…”

“…Prevotella dominant oropharyngeal microbiota was more frequent in healthy adults than in adults with pneumonia, but more frequent in older children with severe pneumonia than in non-severe pneumonia cases. 46,66 Veillonella and Dolosigranulum were frequently sequenced in healthy individuals or patients with less severe pneumonia in upper respiratory tract samples, the latter particularly in young children. 46,66,67,73 Interestingly, despite Moraxella being associated with pneumonia, Moraxella lacunata was significantly more frequent in pediatric viral vs. non-viral pneumonia, and more frequent in controls than in all-cause pneumonia, highlighting the necessary caution in establishing associations based on phylum or genera-level taxonomics.…”

“…We excluded HIV infected patients, as it was object of a recently published review. 3 A total of 25 articles were retained for this section, 13 in adults, [46][47][48][49][50][51][52][53][54][55][56][57][58] and 11 in children. 19,[59][60][61][62][63][64][65][66][67][68][69] An overview of the studies characteristics is summarized in tables 2 (adults) and 3 (children).…”

The role of the local microbial ecosystem in respiratory health and disease

“…as well as other Gram-negative anaerobic species like Leptotrichia and Veillonella spp. is associated with pneumonia [112].…”